Page 24, Figure 12 has been replaced because the American College of Cardiology Foundation/American Heart Association issued a revised clinical practice guideline for the management of ST-elevation myocardial infarction (STEMI) (O'Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Jan 29;127(4):e362-425. Erratum in: Circulation. 2013 Dec 24;128(25):e481. [PMID: 23247304]). This updated guideline recommends that patients with STEMI presenting to a facility not capable of performing percutaneous coronary intervention (PCI) be transferred to a PCI-capable facility if the time from first medical contact to device therapy is anticipated to be 120 minutes or less.

Footnote C of Figure 12 should read: "FMC-to-device ("door-to-balloon") goal for patients being transferred for primary PCI is as soon as possible and ≤120 minutes." A new footnote D should read: "P2Y12 inhibitors: clopidogrel, prasugrel, ticagrelor." In footnote E (formerly footnote D), "90 minutes" should be changed to "120 minutes." Finally, the credit line for Figure 12 should read as follows: "Recommendations based on O'Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Jan 29;127(4):e362-425. Erratum in: Circulation. 2013 Dec 24;128(25):e481. [PMID: 23247304]." (Added June 2015)

Page 28, Key Points: The second Key Point should read: "Patients with ST-elevation myocardial infarction should be treated with percutaneous coronary intervention (PCI) within 120 minutes of first medical contact; if PCI cannot be delivered during this time frame and in the absence of contraindications, thrombolytic therapy should be administered (within 30 minutes of presentation)." (Added June 2015)

Page 38: In Heart Failure, Inpatient Management of Heart Failure, Acute Decompensated Heart Failure, in the first sentence of the last paragraph, the words "or hypovolemic" should be deleted. The sentence should read as follows: "Two vasopressin antagonists are used to treat euvolemic hyponatremia..." Vasopressin antagonists may be used for treatment of euvolemic hyponatremia but are contraindicated in patients with hypovolemic hyponatremia. (Added June 2014)

Page 70, left column, first paragraph: In the last sentence, the phrase "because a compensatory increase in heart rate is expected" should be deleted. The sentence should read: "Rate response in atrial fibrillation should be controlled with conventional medications, but bradycardia should be avoided." (Added January 2013)

Page 89, right column, bottom of the page: In the first sentence of the last paragraph, "CMR imaging" should be "MRI." (Added January 2013)

Page 119: Item 2. This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer A to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. See the ACC/AHA cholesterol management guideline summaries for more information. (Added June 2014)

Page 123, Item 12: This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer C to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. Although the published correct answer C, start eplerenone, is the most appropriate choice among the options listed, it may not be the best first treatment option for the patient described in this item. Although the efficacy of eplerenone is substantiated by the results of the EPHESUS trial cited in the critique, the educational objective of the question was to emphasize the benefit of aldosterone antagonist therapy in specific patients with heart failure or other comorbidities. Eplerenone’s benefits as supported by the study may be offset by this agent’s high cost; spironolactone is an acceptable alternative that could have been used initially in this patient before another aldosterone antagonist such as eplerenone was tried.

In addition, a Cardiovascular Medicine committee member disclosed a relationship with the manufacturer of the agent eplerenone (Pfizer) as part of MKSAP’s conflict of interest disclosure policy. After further postpublication review of MKSAP, the Editors determined that, although the question is technically correct as written, invalidation of item 12 was necessary in our efforts to provide evidence-based medical education without the appearance of bias that models appropriate care and is in alignment with ACP’s emphasis on high-value care. (Added September 2013)

Pages 129-130, Item 38: This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer C to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. Following the publication of MKSAP 16, the American College of Cardiology Foundation/American Heart Association issued a revised clinical practice guideline for the management of ST-elevation myocardial infarction (STEMI) (O'Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Jan 29;127(4):e362-425. Erratum in: Circulation. 2013 Dec 24;128(25):e481. [PMID: 23247304]). This updated guideline recommends that patients with STEMI presenting to a facility not capable of performing percutaneous coronary intervention (PCI) be transferred to a PCI-capable facility if the time from first medical contact to device therapy is anticipated to be 120 minutes or less. This patient can be transferred to a PCI-capable facility in 120 minutes; therefore, option D (transfer for primary PCI) is now correct. (Added June 2015)

Page 150: Item 103. This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer C to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. See the ACC/AHA cholesterol management guideline summaries for more information. (Added June 2014)

Page 161, Item 11: In the first line of the critique, diastolic heart failure should be changed to systolic heart failure: "This patient has decompensated systolic heart failure..." (Added November 2014)

Page 211, Item 114: The last sentence of the first paragraph of the critique should read: "In a normal study without an intracardiac shunt, the bubbles produced in an agitated saline contrast study dissipate in the pulmonary microcirculation and do not opacify the left ventricle." (Added April 2013)

Dermatology

Page 9, Figure 13: The figure legend should be changed to read: "Atopic dermatitis of the popliteal fossa demonstrating characteristic erosions, crusting, and lichenification; the antecubital fossa may also be involved." (Added April 2013)

Page 13: In Pityriasis Rosea, the following should be added after the third sentence: "Trailing scale refers to an area of scaling that follows an advancing border or rash, usually associated with annular lesions such as pityriasis or erythema annulare centrifugum." (Added April 2013)

Page 25: In the second paragraph of the Cellulitis and Erysipelas section, the first sentence should read: "In contrast to cellulitis which involves the deeper layers of the skin (lower dermis, subcutaneous fat, and other structures), erysipelas refers to an infection of the upper dermis and superficial lymphatics." Similarly, the second key point on that page should also be changed. (Added September 2013)

Page 38, Figure 72: The figure legend should be changed to read: "Acral melanomas are found on the palms, soles, and on subungual surfaces typically presenting as black or dark brown irregularly pigmented macules or patches." (Added April 2013)

Pages 45-46: The fourth sentence in Autoimmune Bullous Diseases should read: "Several autoimmune bullous diseases can be associated with systemic disease, including malignancy, and their presence may necessitate further medical evaluation." (Added April 2013)

Page 60, The fourth bullet in Diabetes Mellitus: "Scleroderma" should be "Scleredema." (Added April 2013)

Page 66: In Androgenetic Alopecia, the following sentences should be added at the end of the paragraph: "Finasteride is contraindicated (FDA category X) in pregnant women because it is known to cause birth defects in the male fetus. Women who are or may potentially be pregnant should not take finasteride and should avoid contact with crushed or broken tablets because it can be absorbed through the skin." (Added April 2013)

Page 69: In Onychomycosis, delete the reference to Figure 116 and insert the following: "However, onychomycosis may be difficult to differentiate from other nail disorders such as onycholysis and onychodystrophy that may be seen with systemic diseases (Figure 116)." (Added April 2013)

Page 69, Figure 116. The figure legend should be changed to read: "This patient with psoriatic arthritis has onycholysis and onychodystrophy and is clinically difficult to distinguish from onychomycosis caused by a fungal infection. Before treatment of onychomycosis is instituted, it is important to confirm the diagnosis by potassium hydroxide (KOH) examination of the nail, a fungal culture, or by histologic examination of the nail clippings." (Added April 2013)

Endocrinology and Metabolism

Page 5, Management of Diabetes, Glycemic Monitoring: The third column of Table 6 inadvertently listed incorrect values. The correct values in mmol/L are as follow: 5.4, 7.0, 8.5, 10.2, 11.8, 13.3, 14.9, and 16.5. This table has been corrected in the online version of MKSAP 16. (Added November 2014)

Page 6, Diabetes Mellitus, Management of Diabetes, Cardiovascular Risk: Number 8 in the list appearing after the first paragraph (left hand column) and sentence five of the paragraph beginning after the numbered list (lines 12 through 18 of the second column). See the ACC/AHA cholesterol management guideline summaries for more information. (Added June 2014)

Page 6, Diabetes Mellitus, Management of Diabetes, Cardiovascular Risk: Number 9 on the list appearing after the first paragraph (left hand column) and last paragraph of the section (right-hand column). See the JNC 8 guideline summary for more information. (Added June 2014)

Page 11: In Inpatient Management of Hyperglycemia and Diabetes, the last sentence of the first paragraph should be changed from "For these reasons, measurement of plasma glucose and hemoglobin A1c levels should be routine when most adults are admitted" to "For these reasons, hospital admission provides a good opportunity to screen for the presence of diabetes through measurement of plasma glucose and hemoglobin A1c levels. However, the benefits of this screening are likely greatest in patients with specific risk factors. For example, the United States Preventive Services Task Force (USPSTF) concludes that screening for diabetes in adults with sustained blood pressure greater than 135/80 mm Hg has benefit but that no clear evidence of benefit exists when blood pressures are 135/80 mm Hg or less. Similarly, the ADA, on the basis of expert opinion, recommends consideration of screening patients for impaired fasting glucose, impaired glucose tolerance, or diabetes in persons age 45 years or older, particularly those with a body mass index of 25 or greater; this organization also states that diabetes screening should be considered in persons younger than 45 years who are overweight if they have another risk factor for diabetes, including inactivity, family history of type 2 diabetes, membership in a high-risk ethnic group, gestational diabetes, hypertension, dyslipidemia, impaired fasting glucose, impaired glucose tolerance, or a history of vascular disease." (Added April 2013)

Page 11: In the first sentence, fourth paragraph, and first Key Point of Inpatient Management of Hyperglycemia and Diabetes, the recommended plasma glucose range for critically ill hospitalized patients with hyperglycemia should be changed, according to American College of Physicians guidelines, from 140 to 180 mg/dL (7.8-10.0 mmol/L) to 140 to 200 mg/dL (7.8-11.1 mmol/L). Similarly, the second sentence of the same paragraph about the consensus statement by the American Diabetes Association and the American Association of Clinical Endocrinologists (that recommends maintaining fasting and premeal glucose levels of less than 140 mg/dL [7.8 mmol/L] but no lower than 90 mg/dL [5.0 mmol/L] and random or postprandial levels of less than 180 mg/dL [10.0 mmol/L] in noncritically ill hospitalized patients) should have been followed by the statement: "However, the American College of Physicians recommends not using intensive insulin therapy to strictly control blood glucose levels in noncritically ill hospitalized patients with or without diabetes mellitus, noting that avoiding targets less than 140 mg/dL (7.8 mmol/L) should be a priority because harms are likely to increase at lower blood glucose targets." The second Key Point at the end of this section should also have been followed by this clarification. (Added April 2013)

Page 11: The last sentence of the last paragraph of the Inpatient Management of Hyperglycemia and Diabetes section should read: "For patients who are more critically ill or whose blood glucose level cannot be maintained in target range with subcutaneous insulin, an intravenous insulin (not glucose) infusion, which allows much more rapid adjustments, should be considered..." (Added September 2013)

Page 24: In Disorders of the Pituitary Gland, Hyperprolactinemia and Prolactinomas, Clinical Features and Therapy of Hyperprolactinemia and Prolactinomas, the end of second key point should read "and whose tumor is no longer visible" (not "or whose tumor is no longer visible"). (Added June 2014)

Page 36: In Structural Disorders of the Thyroid Gland, Thyroid Nodules, the first sentence of the third full paragraph in the right-hand column should be replaced with the following: "Patients with nodules greater than 4 cm who have associated worrisome historical findings (such as a history of external radiation to the neck), clinical findings (such as abnormal cervical lymphadenopathy or hoarseness), or radiologic features (see Table 20) but benign results of FNA biopsy can be considered for thyroidectomy." (Added April 2013)

Page 41: In the third sentence of the first paragraph of Description, Causes, and Diagnosis of Adrenal Insufficiency, the word "diminished" should precede the abbreviation "ACTH" ("In contrast, central adrenal insufficiency is caused either by diminished ACTH secretion...") (Added April 2013)

Page 45, Disorders of the Adrenal Glands, Cushing syndrome: In the last sentence on this page (fifth paragraph of section), the phrase "Using a CRH plus desmopressin stimulation test" is incorrect and should be replaced with the phrase "Adding CRH to a low-dose dexamethasone suppression test" for accuracy. (Added June 2014)

Page 89, Item 39: In the table of laboratory values, the seventh line on this page listing "Cortisol, random (1 PM) 2.5 μg/dL" should have included the normal range; this line is now replaced with "Cortisol, random (1 PM) 2.5 μg/dL (normal, > 3 μg/dL [83 nmol/L])" to be clearer. Additionally, the fourth sentence of the critique for this item ("Although the random serum cortisol level..."), which appears on page 119, should be replaced by "The random serum cortisol level is inappropriately low for the degree of hypotension experienced by this patient—especially because hypotension is a strong stimulus for ACTH and cortisol release. Any serum cortisol level (random or 8:00 AM) of 3 µg/dL (83 nmol/L) or less is suggestive of adrenal insufficiency, and no ACTH stimulation test is required for diagnosis. In this setting, if the ACTH level is greater than 100 pg/mL (22 pmol/L), then the diagnosis is primary adrenal insufficiency. A random serum cortisol of greater than 17 µg/dL (469 nmol/L) essentially rules out the diagnosis of adrenal insufficiency, and a level this elevated would be expected with the degree of hypotension in this patient." (Added June 2014)

Page 90, item 45 (see also page 122 for critique). See the ACC/AHA cholesterol management guideline summaries for more information. (Added June 2014)

Page 93, Item 56: In the last line of the left-hand column of this page (second sentence of the question), the phrase "moderate fatigue" should be replaced with the phrase "occasional tiredness." (Added June 2014)

Page 135, Item 75: In the first sentence of the second paragraph at the top of the right-hand column (fourth paragraph of the critique), the word "hypocalcemia" should be replaced by "hypomagnesemia." (Added June 2014)

Page 135, Item 76: The last word of the critique for this item should be "hyperglycemia" not "hypoglycemia." (Added June 2014)

Gastroenterology and Hepatology

Page 38, fourth sentence under Health Care Maintenance for the Patient with Inflammatory Bowel Disease should read: "Immunosuppressed patients should receive influenza vaccination every year and pneumococcal vaccination as recommended by the Advisory Committee on Immunization Practices (ACIP)."

In October 2012, the Advisory Committee on Immunization Practices (ACIP) updated recommendations for pneumococcal vaccination in patients with immunocompromising conditions, anatomic or functional asplenia, cerebrospinal fluid (CSF) leaks, or cochlear implants. Immunocompromising conditions are defined as follows: congenital or acquired immunodeficiency, HIV infection, chronic kidney disease, the nephrotic syndrome, leukemia, lymphoma, Hodgkin disease, generalized malignancy, iatrogenic immunosuppression (such as long-term corticosteroid therapy), solid organ transplant, and multiple myeloma. For adults ≥19 years of age with an immunocompromising condition, functional asplenia, a CSF leak, or cochlear implants who have never received any pneumococcal vaccination, an initial dose of 13-valent pneumococcal conjugate vaccine (PCV-13) should be given, followed by a first dose of 23-valent pneumococcal polysaccharide vaccine (PPSV-23) at least 8 weeks later. A single, second dose of PPSV-23 should be given 5 years after the first PPSV-23 vaccination in those with anatomic or functional asplenia or with an immunocompromising condition. For adults ≥19 years of age with immunocompromising conditions, anatomic or functional asplenia, CSF leaks, or cochlear implants who have previously received at least one dose of PPSV-23, a single PCV-13 dose should be given ≥1 year after their last PPSV-23 immunization. All patients who have ever received a PPSV-23 vaccination should receive another dose of PPSV-23 at age 65 years, or later if at least 5 years have elapsed since their last PPSV-23 dose. (Added April 2013)

Page 59, third paragraph under Wilson Disease: The second-to-last sentence should read, "Kayser-Fleischer rings, noted on ophthalmologic examination, indicate copper deposition in the Descemet membrane of the cornea." (Added June 2014)

Page 63, Table 32, second row, second column: The starting dose of nadolol should be 40 mg orally once a day (rather than twice a day). (Added June 2014)

Page 69, third sentence under Immunizations should read: "Pneumococcal vaccination should be given according to the recommendations of the Advisory Committee on Immunization Practices (ACIP) for immunosuppressed patients, and tetanus toxoid should be given every 10 years." See new information above clarifying the use of pneumococcal vaccination in patients with immunocompromising conditions. (Added April 2013)

Page 88, Item 5: The fourth sentence should read, "She has a history of type 1 diabetes mellitus for which she takes insulin glulisine and insulin detemir." (Added June 2015)

Page 98, Item 48, the normal range for insulin should appear at the end of the second sentence. The sentence should read, "During hospitalization, she developed neuroglycopenic symptoms after 8 hours of fasting associated with a plasma glucose level of 30 mg/dL (1.7 mmol/L) and a corresponding insulin level of 8 μU/mL (58 pmol/L) (normal range, 2.6-24.9 μU/mL [19-180 pmol/L])." (Added June 2015)

Page 117, Item 15: In the first paragraph of the critique, the second-to-last sentence should read: "Thus, predominant heartburn or regurgitation symptoms should be categorized as GERD rather than dyspepsia." (Added January 2013)

Page 123, Item 30, second paragraph of critique, third sentence: See new information above clarifying the use of pneumococcal vaccination in patients with immunocompromising conditions. (Added April 2013)

Page 124, critique of Item 32: The first paragraph of the critique should read: "In this patient with chronic hepatitis C virus (HCV) infection and advanced fibrosis, antiviral therapy is indicated. Chronic HCV infection is often progressive and may result in cirrhosis and hepatocellular carcinoma. The goal of HCV treatment is sustained virologic response (SVR), defined as loss of HCV RNA 6 months after completion. SVR results in improved patient outcomes, including a decrease in all-cause mortality. Patients with cirrhosis are less likely to achieve SVR than those without cirrhosis. The treatment of HCV is evolving rapidly. New oral direct-acting antiviral combinations are likely to be approved in 2014 by the FDA and will result in a decrease in the use of peginterferon." The Key Point should read: "The treatment of hepatitis C is evolving rapidly; new oral direct-acting antiviral combinations are likely to be approved by the FDA and will result in a decrease in the use of peginterferon." (Added November 2014)

Page 150, critique of Item 90: The fourth sentence should read, "Methylnaltrexone, which is a μ-opioid–receptor antagonist..." (Added June 2015)

General Internal Medicine

Page 5, Table 3: In the "Positive likelihood ratio (LR+)" row, the entry in the "Definition" column should be changed to read: "The likelihood that a positive test result would be expected in a patient with the disease compared with the likelihood that a positive test result would be expected in a patient without a disease." (Added November 2014)

Page 14, Pneumococcal Disease (text and Table 8 ): The following new information clarifies the use of pneumococcal vaccination in patients with immunocompromising conditions.

In October 2012, the Advisory Committee on Immunization Practices (ACIP) updated recommendations for pneumococcal vaccination in patients with immunocompromising conditions, anatomic or functional asplenia, cerebrospinal fluid (CSF) leaks, or cochlear implants. Immunocompromising conditions are defined as follows: congenital or acquired immunodeficiency, HIV infection, chronic kidney disease, the nephrotic syndrome, leukemia, lymphoma, Hodgkin disease, generalized malignancy, iatrogenic immunosuppression (such as long-term corticosteroid therapy), solid organ transplant, and multiple myeloma. For adults ≥19 years of age with an immunocompromising condition, functional asplenia, a CSF leak, or cochlear implants who have never received any pneumococcal vaccination, an initial dose of 13-valent pneumococcal conjugate vaccine (PCV-13) should be given, followed by a first dose of 23-valent pneumococcal polysaccharide vaccine (PPSV-23) at least 8 weeks later. A single, second dose of PPSV-23 should be given 5 years after the first PPSV-23 vaccination in those with anatomic or functional asplenia or with an immunocompromising condition. For adults ≥19 years of age with immunocompromising conditions, anatomic or functional asplenia, CSF leaks, or cochlear implants who have previously received at least one dose of PPSV-23, a single PCV-13 dose should be given ≥1 year after their last PPSV-23 immunization. All patients who have ever received a PPSV-23 vaccination should receive another dose of PPSV-23 at age 65 years, or later if at least 5 years have elapsed since their last PPSV-23 dose. (Added April 2013)

Page 41, Table 19: The direction of the nystagmus produced by the Dix-Hallpike maneuver is inaccurately described. In the "Direction of Nystagmus" row, the entry in the "Peripheral Disease" column should read "Unidirectional, mixed upbeat and torsional with a small horizontal component," and the entry in the "Central Disease" column should read "Direction of nystagmus may depend on direction of gaze; may be purely vertical or horizontal without a torsional component." (Added June 2015)

Page 47, top of first column: The last sentence of the section "Diagnostic Evaluation of Syncope" should be deleted, and replaced with new text.

The sentence that is deleted is as follows: "Tilt-table testing should be reserved for patients with suspected neurocardiogenic syncope not confirmed by history and physical examination, for those with recurrent syncopal episodes, and for patients suspected of having arrhythmogenic syncope or who have a high risk profile for cardiovascular events in whom previous testing has not been revealing."

The new text that is inserted is as follows: "Tilt-table testing should be reserved for patients with recurrent episodes of syncope in the absence of known heart disease or in patients with documented heart disease in whom a cardiac cause has been excluded. Tilt-table testing may also have a role in evaluating patients in whom documenting neurocardiogenic syncope is important (such as in high-risk occupational settings), and differentiating the cause of syncope from neurologic (such as seizure) or psychiatric etiologies." (Added April 2013)

Page 65, first column, sixth line of text: The following sentence should be inserted after the sentence ending "... with multiple medications": "However, because warfarin is also metabolized by CYP2C9, both fluvastatin and rosuvastatin have been associated with increases in the INR in warfarin-treated patients; concurrent use of either of these medications with warfarin should be avoided or monitored closely." (Added April 2013)

Page 66: In Dyslipidemia, Management of Dyslipidemias, Management of Hypertriglyceridemia, the effects of fibrate therapy on LDL cholesterol levels has been clarified. The 5th and 6th sentences of the paragraph should read: "Fibrates are also effective for reducing triglycerides and increasing HDL cholesterol levels (changes of 40%-60% and 15%-25%, respectively), but in persons with familial hypertriglyceridemia, they can raise LDL cholesterol levels by up to 30%. Thus, fibrate monotherapy may be ineffective in these patients for achieving non-HDL cholesterol goals." Additionally, in Table 26 (page 65), in the Fibrates row, the entry in the second column should read "LDL cholesterol ↓ 5%-20% (↑ in some patients with elevated TGs) . . . " and the entry in the fourth column should read "Most effective agents for reducing TGs, but may raise LDL cholesterol in patients with familial hypertriglyceridemia. . . . " (Added June 2014)

Page 86: In Intrauterine Devices, in the last sentence of the paragraph, "within 7 days" should be changed to "within 5 days." (Added April 2013)

Page 89, first column, Nonhormonal Therapy: The following sentence should be added after the 2nd sentence of the paragraph: "Different antidepressant agents appear to have variable efficacy for this use: Venlafaxine, desvenlafaxine, and paroxetine have been demonstrated to be effective in some women; in contrast, few studies have shown efficacy with fluoxetine, sertraline, or citalopram." (Added April 2013)

Page 143, Item 2: In the first sentence, "left hand" should be "right hand." (Added January 2013)

Page 144, Item 7: This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer D to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission.

Because the patient was not specifically noted to have had an erythrocyte sedimentation rate (ESR) performed as part of her prior laboratory studies, and obtaining an ESR is reasonable to assess for the presence of an active inflammatory process as the cause of chronic fatigue, this option would be potentially correct. (Added April 2013)

Page 148, Item 26: In the second paragraph of the stem, the phrase "left arm" should be replaced with the phrase "right arm." (Added November 2014)

Page 152: Item 41. This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer C to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. See the ACC/AHA cholesterol management guideline summaries for more information. (Added June 2014)

Page 153, Item 47: The lead-in question should be changed from "Which of the following should be recommended before surgery?" to "Which of the following interventions is most likely to reduce this patient's risk of perioperative pulmonary complications?" (Added September 2013)

Page 164, Item 98: The second sentence of the second paragraph should read: "With the Dix-Hallpike maneuver, she develops mixed upbeat-torsional nystagmus and nausea after 15 seconds." Additionally, in the first paragraph of the critique, the last sentence should read: "A positive test results in mixed upbeat-torsional nystagmus with latency 2 to 40 seconds and duration less than 1 minute with reproduction of symptoms that will fatigue and habituate." (Added June 2015)

Page 175, Item 148: At the end of the first paragraph of the stem, the sentence "Her only medication is tiotropium" should be changed to "She is on no medications." (Added April 2013)

Page 199, Item 42: In the first paragraph of the critique, the last sentence should read, "Older men and men who engage in insertive anal intercourse, wherein the urethra is exposed to the bacterial environment of the anorectal area, are more susceptible to Escherichia coli, Enterobacteriaceae, and pseudomonal infection." (Added June 2015)

Page 250, Item 151: The third paragraph of the critique should be replaced with the following: "The U.S. Preventive Services Task Force (USPSTF) recommends annual screening for lung cancer with low-dose CT in adults aged 55 to 80 years who have a 30-pack-year smoking history and currently smoke or have quit within the past 15 years. Plain chest radiography is not recommended to screen for lung cancer in any population. Although this patient is a former smoker, he has only a 2-pack-year smoking history and quit smoking more than 15 years ago; therefore, lung cancer screening is not indicated." (Added November 2015)

Page 253, Item 159: In the third sentence of the first paragraph of the critique, "chronic cardiovascular disease (including hypertension)" should be changed to "chronic cardiovascular disease (including heart failure and cardiomyopathies, excluding hypertension)." (Added November 2015)

Hematology and Oncology

Page 17, fourth paragraph in Waldenström Macroglobulinemia: The first sentence should be changed from "Diagnosis requires demonstration of lymphoplasmacytic lymphoma comprising 10% or more of the bone marrow cellularity and the presence of an IgM M protein" to "Diagnosis requires demonstration of lymphoplasmacytic lymphoma (a neoplastic infiltrate consisting of lymphocytes, plasmacytoid lymphocytes, plasma cells, and immunoblasts) comprising 10% or more of the bone marrow cellularity and the presence of an IgM M protein." (Added January 2013)

Page 28, The first sentence of the first full paragraph should read: "The deletion of three α genes (--/-α) leads to hemoglobin H (β4) disease, which may be associated with severe anemia and clinical sequelae, including heart failure and hypoxia, and is identifiable on hemoglobin electrophoresis." (Added January 2013)

Page 35, the third sentence in first paragraph in Other Causes of Hemolysis should read: "Babesiosis may also lead to severe hemolytic anemia in patients with previous splenectomy or functional asplenia and should be suspected in patients with hemolysis after recent travel to high-incidence areas, such as states in the northeast United States (including Nantucket Island and Cape Cod), and the upper midwestern states." (Added September 2013)

Page 65, the first sentence of the second paragraph under Thromophilia and Venous Thromboembolism in Pregnancy, has been clarified to state, "Pregnancy is associated with normal total protein S levels but (because of changes in protein binding) decreases in the more biologically active free protein S antigen and resulting protein S activity, and increases in factor VIII..." (Added June 2015)

Page 69, Table 37: The last row of the table was incorrect; it has been split into two rows and revised to reflect the following: Imatinib and Gefitinib are both tyrosine kinase inhibitors, but only gefitinib targets epidermal growth factor receptor. Imatinib targets BCR-ABL in chronic myeloid leukemia and k-KIT in gastrointestinal stromal tumors. (Added November 2014)

Page 72, right-hand column, the third full paragraph, first sentence AND page 219, Item 142, fifth sentence of critique should read: "Postmenopausal women with hormone receptor–positive breast cancer should take a 5-year course of an aromatase inhibitor as primary treatment or for an additional 5 years after completing a 5-year course of tamoxifen therapy. In women who are initially treated with tamoxifen, an aromatase inhibitor may be started following 2 to 3 years of tamoxifen therapy to complete a total of 5 years of hormonal therapy." (Added January 2013)

Page 171, Item 28: The second sentence of critique should read: "This patient has cobalamin deficiency as evidenced by elevations in homocysteine and methylmalonic acid, with a typical peripheral blood smear." (Added January 2013)

Page 172, Item 31: In the first paragraph of the critique, regarding the Mentzer index, "fluid liters" should be changed to "femtoliters." (Added November 2014)

Page 180, Item 48: In the last paragraph of the critique, the inheritance pattern of protein C deficiency is inaccurately described. The first sentence of this paragraph should be replaced by the following: "Both antithrombin deficiency and protein C deficiency are inherited in an autosomal dominant pattern." (Added November 2014)

Page 186, Item 62: In the first paragraph of the critique, listing the criteria for diagnosis of acute chest syndrome in sickle cell disease patients: "temperature less than 38.5 °C (101.3 °F)" should be changed to "temperature greater than or equal to 38.5 °C (101.3 °F)." (Added November 2014)

Page 186, Item 62: The first sentence of third paragraph should read: "Furosemide may be helpful in those patients who are hypervolemic, but there is no clinical evidence to support this diagnosis in this patient." (Added January 2013)

Page 189, Item 69: The following sentence was deleted from the 4th paragraph of the critique: "Teratomas may be evident on plain chest radiograph or CT scan." The sentence is factually correct, but may be confusing in the context of the question. (Added November 2014)

Page 208, Item 114: This question has been invalidated. The correct answer is B, not C as it appears in print. Please select answer B to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. (Added January 2013; modified June 2014)

Page 212, Item 124: In the last sentence of the first paragraph of the critique, cefepime is a fourth-generation, not a third-generation, cephalosporin. (Added September 2013)

Page 213, Item 127: The second sentence of the second paragraph of the critique should be changed. Radiation is not recommended for patients with early-stage bladder cancer that does not invade the muscle (original version stated "does not invade the bladder"). (Added November 2014)

Infectious Disease

Page 7: In the left-hand column, third paragraph, the sentence "For abscesses in the early cerebritis stage (that is, the earliest stage of purulent brain infection when there is little or no enhancement on neuroimaging) or when all the abscesses are smaller than 2.5 cm, the largest lesion should be aspirated for diagnosis and microbiologic identification" should be replaced with the following sentences: "Diagnosis is more challenging in the early cerebritis stage (that is, the earliest stage of purulent brain infection when there is little or no enhancement on neuroimaging). If multiple focal lesions develop measuring less than 2.5 cm in an area of suspected infection, the largest lesion present should be aspirated for diagnosis and microbiological identification." (Added April 2013)

Page 56: In the first paragraph, the sentence "Conjugate vaccines are preferred to polysaccharide vaccines in these patients" should be deleted. The following new information clarifies the use of pneumococcal vaccination in patients with immunocompromising conditions.

In October 2012, the Advisory Committee on Immunization Practices (ACIP) updated recommendations for pneumococcal vaccination in patients with immunocompromising conditions, anatomic or functional asplenia, cerebrospinal fluid (CSF) leaks, or cochlear implants. Immunocompromising conditions are defined as follows: congenital or acquired immunodeficiency, HIV infection, chronic kidney disease, the nephrotic syndrome, leukemia, lymphoma, Hodgkin disease, generalized malignancy, iatrogenic immunosuppression (such as long-term corticosteroid therapy), solid organ transplant, and multiple myeloma. For adults ≥19 years of age with an immunocompromising condition, functional asplenia, a CSF leak, or cochlear implants who have never received any pneumococcal vaccination, an initial dose of 13-valent pneumococcal conjugate vaccine (PCV-13) should be given, followed by a first dose of 23-valent pneumococcal polysaccharide vaccine (PPSV-23) at least 8 weeks later. A single, second dose of PPSV-23 should be given 5 years after the first PPSV-23 vaccination in those with anatomic or functional asplenia or with an immunocompromising condition. For adults ≥19 years of age with immunocompromising conditions, anatomic or functional asplenia, CSF leaks, or cochlear implants who have previously received at least one dose of PPSV-23, a single PCV-13 dose should be given ≥1 year after their last PPSV-23 immunization. All patients who have ever received a PPSV-23 vaccination should receive another dose of PPSV-23 at age 65 years, or later if at least 5 years have elapsed since their last PPSV-23 dose. (Added April 2013)

Page 81: After the last sentence of the Treatment section, the following sentence defining antibiotic lock therapy was added: "Antibiotic lock therapy involves the instillation of a highly concentrated antibiotic solution into an intravenous catheter to facilitate sterilization in order to treat a catheter-related blood stream infection." (Added April 2013)

Page 88: In the first paragraph under Immunizations and Prophylaxis for Opportunistic Infections, the word "polysaccharide" should be deleted. See new information above clarifying the use of pneumococcal vaccination in patients with immunocompromising conditions. (Added April 2013)

Page 124, Item 53: The sentence "A radiograph of the left foot reveals soft tissue swelling with erosion of the cortex at the head of the metatarsal bone beneath the site of the ulceration" was changed to "A radiograph of the left foot indicates no subcutaneous gas or foreign bodies." (Added April 2013)

Page 124, Item 54. This question has been invalidated as a result of new data/updated recommendations that are relevant to the question. Please select answer C to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. Based on recent published data and recommendations, the treatment regimen of zidovudine, lamivudine, and lopinavir-ritonavir is no longer the most effective/best therapy for pregnant women newly diagnosed with HIV. Recommendations now indicate a dual nucleoside reverse transcriptase inhibitor (NRTI) combination (abacavir-lamivudine, tenofovir disoproxil fumarate (tenofovir)-emtricitabine or lamivudine, or zidovudine-lamivudine) in combination with either a ritonavir-boosted protease inhibitor (atazanavir/ritonavir or darunavir/ritonavir), a non-NRTI (efavirenz initiated after 8 weeks of pregnancy) or an integrase inhibitor (raltegravir). (Added November 2015)

Page 132, Item 86: The first sentence of the question should read: "A 25-year-old woman undergoes follow-up evaluation of an episode of anaphylaxis that occurred 3 weeks ago following a transfusion of packed red blood cells after trauma resulting from a motor vehicle collision." (Added January 2013)

Page 152, Item 29: The second sentence of the last paragraph of the critique is incorrect. It should read, "In addition, reactive arthritis tends to present as an asymmetric oligoarthritis. Although reactive arthritis and disseminated gonococcal infection may present with an asymmetric oligoarthritis, reactive arthritis may be accompanied by skin findings such as an associated rash and keratoderma blennorrhagica." (Added November 2014; Revised November 2015)

Page 180, Item 92: The second sentence of the first paragraph of the critique should state that the pre-engraftment phase is <30 days after transplantation, not >30 days. (Added November 2014)

Page 134, Item 97: This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Specifically, both options (A) avoidance of tap water and (E) prophylactic rifaximin could be construed as correct. As stated in the critique, although the avoidance of tap water has been shown to confer only a mild benefit, this practice continues to be recommended for travelers by the Centers for Disease Control and Prevention. Therefore, this could be considered a correct option. Please select answer E to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. (Added April 2013)

Page 180, Item 92. The last sentence of the first paragraph of the critique should be changed to "This emphasizes the need for diligent administration of pneumococcal vaccines in solid organ transplant patients who are by definition considered to have an immunocompromising condition." See new information above clarifying the use of pneumococcal vaccination in patients with immunocompromising conditions. (Added April 2013)

Page 186, Item 106: The second paragraph of the critique of item 106 was changed to the following: "Although continuous antibiotic prophylaxis is a treatment option, in women with recurrent urinary tract infections temporally related to sexual intercourse, postcoital prophylaxis is generally the preferred approach because of patient convenience, a decreased overall exposure to antibiotics, and a lower risk of development of antimicrobial resistance." (Added April 2013)

Page 4, Table 3: In the Comments column of the Leukocytes row, the original text "Lower levels can be abnormal" has been replaced with "The presence of any leukocytes may be abnormal depending on clinical circumstances." (Added April 2013)

Page 4: The medication levodopa does not contain a sulfhydryl group as indicated, but levodopa metabolites in the urine may react with nitroprusside, which is typically used to detect the presence of acetoacetic acid, causing a false-positive result for urinary ketones. (Added June 2014)

Page 6, Table 6: In the "Total Protein" row, the normal value for 24-hour excretion is <200 mg/24 h, and the value for albuminuria or clinical proteinuria is ≥200 mg/24 h. (Added September 2013)

Page 17, Hypernatremia: The second sentence of the first paragraph states "Therapy is then directed toward correcting the hyponatremia based on estimating the water deficit..." This sentence should read "Therapy is then directed toward correcting the hypernatremia based on estimating the water deficit..." (Added January 2013)

Page 24, Lactic Acidosis: This section states the following: "Lactic acidosis, the most common form of increased anion gap metabolic acidosis, is defined as a serum lactate level greater than 4 mg/dL (0.44 mmol/L)." The unit of measure, mg/dL, is incorrect, and should be meq/L (mmol/L). Because most laboratories no longer report lactate levels in mg/dL (mmol/L), MKSAP will report the levels as meq/L (mmol/L) in the future to avoid this discrepancy. (Added June 2015)

Page 79: Hypertensive Disorders Associated with Pregnancy, Preeclampsia, Prevention and Treatment. See the JNC 8 guideline summary for more information. (Added June 2014)

Page 83: Prevention of Progression, Hypertension. See the JNC 8 guideline summary for more information. (Added June 2014)

Page 85: Prevention of Progression, Proteinuria. See the JNC 8 guideline summary for more information. (Added June 2014)

Page 90, Special Considerations, Vaccination: In the second paragraph of this section, the phrase "and at 5-year intervals" has been deleted. The following new information clarifies the use of pneumococcal vaccination in patients with immunocompromising conditions.

In October 2012, the Advisory Committee on Immunization Practices (ACIP) updated recommendations for pneumococcal vaccination in patients with immunocompromising conditions, anatomic or functional asplenia, cerebrospinal fluid (CSF) leaks, or cochlear implants. Immunocompromising conditions are defined as follows: congenital or acquired immunodeficiency, HIV infection, chronic kidney disease, the nephrotic syndrome, leukemia, lymphoma, Hodgkin disease, generalized malignancy, iatrogenic immunosuppression (such as long-term corticosteroid therapy), solid organ transplant, and multiple myeloma. For adults ≥19 years of age with an immunocompromising condition, functional asplenia, a CSF leak, or cochlear implants who have never received any pneumococcal vaccination, an initial dose of 13-valent pneumococcal conjugate vaccine (PCV-13) should be given, followed by a first dose of 23-valent pneumococcal polysaccharide vaccine (PPSV-23) at least 8 weeks later. A single, second dose of PPSV-23 should be given 5 years after the first PPSV-23 vaccination in those with anatomic or functional asplenia or with an immunocompromising condition. For adults ≥19 years of age with immunocompromising conditions, anatomic or functional asplenia, CSF leaks, or cochlear implants who have previously received at least one dose of PPSV-23, a single PCV-13 dose should be given ≥1 year after their last PPSV-23 immunization. All patients who have ever received a PPSV-23 vaccination should receive another dose of PPSV-23 at age 65 years, or later if at least 5 years have elapsed since their last PPSV-23 dose. (Added April 2013)

Page 93, Special Considerations in Transplant Recipients, Vaccinations: In the second sentence of this section, "every 5 years" has been deleted. See new information above clarifying the use of pneumococcal vaccination in patients with immunocompromising conditions. (Added April 2013)

Page 102, Item 12: The third sentence of the second paragraph has been changed to "An unchanged systolic crescendo-decrescendo murmur is noted at the right upper sternal border." Also, the lead-in question has been changed to "Which of the following is the most appropriate next step in management of this patient's blood pressure?" (Added November 2014)

Page 107, Item 29: This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer A to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. This item has been excluded because the patient is currently taking simvastatin, and adding diltiazem would cause a class D drug-drug interaction. (Added June 2014)

Page 108, Item 31. This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer A to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. Based on more recent published data and recommendations, the use of post-chelation testing has been called into question and cannot be recommended routinely; patients with suspected lead nephrotoxicity with normal blood lead levels should be referred to a clinician with expertise in heavy metal toxicity for further evaluation. (Added November 2015)

Page 113, Item 48: This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer C to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission.

This item has been excluded because of inconsistencies in the normal values of 24-hour protein excretion given in the text, Table 6, and this question's critique. The normal value for 24-hour protein excretion is <200 mg/24 h. (Added September 2013)

Page 113, Item 49: This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer C to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. See the JNC 8 guideline summary for more information. (Added June 2014)

Page 121, Item 75: In the second paragraph of the Stem, the sentence "There is abdominal guarding" should be deleted. Although abdominal guarding is occasionally noted to be caused by nephrolithiasis, it is not considered a "classic" finding and is more commonly associated with peritoneal inflammation (which usually does not occur with kidney stones). (Added April 2013)

Neurology

Page vi: The first sentence under the heading "Permission/Consent for Use of Figures Shown in MKSAP 16 Neurology Multiple-Choice Questions" should read "The figure shown in Self-Assessment Test item 7..." (not "item 8" as listed). (Added January 2013)

Page xi (Neurology High-Value Care Recommendations): The third bullet on the right-hand side of the page should end "(see Item 7)" (not Item 8). Similarly, the fifth bullet should end "(see Item 8)" (not Item 7). (Added January 2013)

Page 11, Head Injury, Concussive Head Injury: In March 2013, after publication of MKSAP 16, the American Academy of Neurology published a summary of its updated evidence-based guideline on the evaluation and management of concussion in sports (Giza CC, Kutcher JS, Ashwal S, et al. Summary of evidence-based guideline update: Evaluation and management of concussion in sports: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013 March 18 [Epub ahead of print] [PMID: 23508730]). This guideline updates assessment of risk factors for concussion, assessment of concussion, and short- and long-term management of concussion, including evaluation for return to play for sports-associated concussion. This supersedes the information contained in MKSAP 16 Neurology. See this article and also http://www.aan.com/go/practice/concussion for fuller information on this updated guideline. (Added September 2013)

Page 27, Ischemic Stroke, Large Artery Atherosclerosis. See the JNC 8 guideline summary for more information. (Added June 2014)

Page 30, Acute Ischemic Stroke, Treatment, Thrombolysis. In the second full paragraph of the first column of this page (third paragraph of "Thrombolysis"), the second sentence through the end of the paragraph should be replaced with the following: "These techniques include local delivery of the thrombolytic agent at the site of a vascular occlusion or mechanical thrombectomy. Both methods have been shown to improve recanalization rates. A previous study showed intra-arterial thrombolytic agents to be superior to intravenous heparin alone if started within 6 hours of stroke onset in patients with large-vessel occlusions. However, subsequent clinical trials have not shown improved outcomes when catheter-based therapies are added to intravenous thrombolysis or a benefit in using intra-arterial therapies alone compared with intravenous thrombolysis. Further, no findings with neuroimaging have been identified that predict a favorable response to intra-arterial therapies. Therefore, intravenous thrombolysis is considered first-line therapy for patients with acute ischemic stroke seen within 4.5 hours of stroke onset. Mechanical thrombectomy remains a reasonable alternative for patients seen in this time frame who have an occlusion of a large intracranial artery but have a contraindication to thrombolytic therapy." (Added September 2013)

Page 73, Neuromuscular Disorders, Treatment of Neuropathic Pain: The first full sentence in the second column of this page has been modified slightly to read "Duloxetine and gabapentin are generally well tolerated but can be associated with weight gain and drowsiness; duloxetine also is more expensive." (Added November 2014)

Page 89, Item 10 (see also page 114 for critique). See the JNC 8 guideline summary for more information. (Added June 2014)

Page 89, Item 11: This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer B to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. This item has been excluded because the American Academy of Neurology (AAN) recently published a summary of its updated evidence-based guideline on the evaluation and management of concussion in sports (Giza CC, Kutcher JS, Ashwal S, et al. Summary of evidence-based guideline update: Evaluation and management of concussion in sports: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013 March 18 [Epub ahead of print] [PMID: 23508730]) that outlines a more individualized approach to the athlete with a concussion and makes specifying a particular time period to exclude an athlete from competition problematic. See this articles and also http://www.aan.com/go/practice/concussion for fuller information on this updated guideline. (Added September 2013)

Page 91, Item 17 (see also page 118 for critique): This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer A to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. See the ACC/AHA cholesterol management guideline summaries for more information. (Added June 2014)

Page 94, item 30 (see also page 123 for critique): This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer E to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. "Reassurance" was replaced by "Continued clinical observation" as the answer because of a concern that the original option could be misinterpreted as suggesting that no further monitoring or possible subsequent evaluation of the patient's symptoms would be indicated. Additionally, invalidation of the question was supported by a lack of consensus about treatment of patients with memory loss. (Added June 2014)

Page 100, Item 55 (see also page 134 for critique): This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer A to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. See the ACC/AHA cholesterol management guideline summaries for more information. (Added June 2014)

Page 101, Item 62 (see also page 137 for critique). See the ACC/AHA cholesterol management guideline summaries for more information. (Added June 2014)

Page 103, Item 73 (see also page 142 for critique). See the ACC/AHA cholesterol management guideline summaries for more information. (Added June 2014)

Page 106, Item 81: In the first line on this page (fourth paragraph of the item), the word "right" should be replaced with the word "left"" ("...shows a left thalamic intracerebral hemorrhage..."). (Added September 2013)

Page 106, Item 86: In the first sentence of the question, the phrase "...is evaluated for a 60-minute episode of..." should be replaced with the phrase "...is evaluated 1 day after experiencing a 60-minute episode of..." In the third sentence of the critique, which appears on page 148, the phrase "whose ABCD2 scores are 3 or greater" should be followed by the phrase "within 72 hours of symptom onset." (Added January 2013)

Page 108, Item 93, and page 151: In options C and D of this question, the phrase “Twice yearly” replaces the word “Biannual,” which was used to mean occurring twice a year. Although this usage is correct, the potential for confusion exists because the term also has a secondary definition of “occurring every two years.” The word “biannual” also has been changed to “twice yearly” in the first sentence of the first paragraph and the first sentence of the fourth paragraph of the critique. (Added June 2014)

Page 143, Item 74: In the first paragraph of the critique, the fifth sentence ("Inhibitors include macrolides...") should be replaced with the following sentence: "Drugs that strongly inhibit cytochrome P3A4 include macrolides, protease inhibitors, and azole antifungals (such as itraconazole); although fibric acid derivatives are only weak inhibitors of the cytochrome pathway, they are independently associated with muscle toxicity, particularly when administered concurrently with certain statin medications." (Added September 2013)

Page 149, Item 87: In the first full paragraph on this page (third paragraph of the critique), the phrase "proximally to distally" in line 5 should be replaced with "distally to proximally." (Added September 2013)

Pulmonary and Critical Care Medicine

Page 25: The second sentence under Other Agents should read: "Mucolytic agents (mucokinetic, mucoregulatory) may provide minor benefit to a few patients with viscous sputum; however, their use cannot currently be recommended." (Added April 2013)

Page 25, Vaccines, second sentence: Guidelines on pneumococcal vaccination have been updated.

In October 2012, the Advisory Committee on Immunization Practices (ACIP) updated recommendations for pneumococcal vaccination in patients with immunocompromising conditions, anatomic or functional asplenia, cerebrospinal fluid (CSF) leaks, or cochlear implants. Immunocompromising conditions are defined as follows: congenital or acquired immunodeficiency, HIV infection, chronic kidney disease, the nephrotic syndrome, leukemia, lymphoma, Hodgkin disease, generalized malignancy, iatrogenic immunosuppression (such as long-term corticosteroid therapy), solid organ transplant, and multiple myeloma. For adults ≥19 years of age with an immunocompromising condition, functional asplenia, a CSF leak, or cochlear implants who have never received any pneumococcal vaccination, an initial dose of 13-valent pneumococcal conjugate vaccine (PCV-13) should be given, followed by a first dose of 23-valent pneumococcal polysaccharide vaccine (PPSV-23) at least 8 weeks later. A single, second dose of PPSV-23 should be given 5 years after the first PPSV-23 vaccination in those with anatomic or functional asplenia or with an immunocompromising condition. For adults ≥19 years of age with immunocompromising conditions, anatomic or functional asplenia, CSF leaks, or cochlear implants who have previously received at least one dose of PPSV-23, a single PCV-13 dose should be given ≥1 year after their last PPSV-23 immunization. All patients who have ever received a PPSV-23 vaccination should receive another dose of PPSV-23 at age 65 years, or later if at least 5 years have elapsed since their last PPSV-23 dose. (Added April 2013)

Page 84, the last sentence under Hyperglycemia should read, "Therefore, based on this data, the ACP Clinical Practice Guideline for Use of Intensive Insulin Therapy for the Management of Glycemic Control in Hospitalized Patients recommends that, following initial stabilization, patients with severe sepsis and hyperglycemia who are admitted to the ICU should receive insulin therapy to achieve a plasma glucose level between 140 and 200 mg/dL (7.8 and 11.1 mmol/L)." The ACP Clinical Practice Guideline can be found here: http://annals.org/article.aspx?articleid=746815. (Added April 2013)

Page 89, the fifth sentence under Alcohols should be deleted and the following should be inserted in its place: "As withdrawal becomes more severe, patients may experience seizures and/or hallucinations, usually within 12 to 24 hours of abstinence. Delirium tremens is a systemic syndrome characterized by hypertension, tachycardia, diaphoresis, fever, disorientation, and hallucinations." (Added April 2013)

Page 110, Item 39: Despite no clinical evidence of active infection in this patient (negative imaging and sputum culture), many clinicians would also treat with a course of empiric broad-spectrum antibiotics for possible pulmonary infection in addition to high-dose glucocorticoids, as suggested in the critique, despite a lack of clear evidence that such treatment is beneficial. (Added June 2014)

Page 114, Item 54: The stem originally stated "...she has been waking up at night at least once a week with asthma symptoms that require her inhaler." The phrase "at least" has been deleted to remove ambiguity. The patient has mild persistent asthma and therefore would not be waking more than once per week. (Added November 2015)

Page 117, Item 65: This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer C to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. Following the publication of MKSAP 16, the American College of Chest Physicians issued a revised clinical practice guideline for the diagnosis and management of lung cancer (Detterbeck FC, Lewis SZ, Diekemper R, Addrizzo-Harris D, Alberts WM. Executive Summary: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):7S-37S. [PMID: 23649434]). These updated guidelines recommend review of prior imaging, if available, in a patient with a pulmonary nodule. In a patient with a solid, indeterminate nodule that shows clear evidence of malignant growth on serial imaging, nonsurgical biopsy and/or surgical resection is recommended unless specifically contraindicated. (Added April 2013 and updated September 2013)

Page 119, Item 72, the last sentence of the first paragraph should read, "She notes a 2-month history of new stiffness and mild pain in her joints, for which she takes NSAIDs as needed." (Added April 2013)

Page 172, critique of Item 95, second sentence: "...(2) postbronchodilator total lung capacity greater than 150% and residual volume greater than 100% of predicted..." should read, "...(2) postbronchodilator total lung capacity greater than 100% and residual volume greater than 150% of predicted..." (Added April 2013)

Page 172, critique of Item 96, third paragraph: The second sentence should read, "Chest examination will reveal severely decreased breath sounds with or without wheezing and a prolonged expiratory to inspiratory ratio." (Added June 2014)

Rheumatology

Page 14: Tocilizumab is incorrectly listed as a chimeric monoclonal antibody; this agent is a humanized monoclonal antibody. (Added September 2013)

Page 30: In Psoriatic Arthritis, the callout for Figure 14 has been deleted from the third paragraph of this section and moved to the second paragraph as follows: "Nails should be examined for pitting or onycholysis (Figure 13 and Figure 14)." (Added April 2013)

Page 58: In the second paragraph of Management, Pharmacologic Therapy, the second sentence "Those with arthralgia or tenosynovitis rather than a frank septic arthritis can be transitioned to oral therapy with ciprofloxacin after symptoms subside" has been deleted.

The following should appear after "Treatment is usually continued for 7 to 14 days depending on the severity of illness": "Although parenteral antibiotics have traditionally been changed to an oral agent following an initial response to therapy to complete a full treatment course, increasing resistance to oral antibiotics has limited their effectiveness for this use. Fluoroquinolones (including ciprofloxacin) are no longer recommended for either initial or step-down therapy for disseminated gonococcal infection. Cefixime is a reasonable alternative for oral therapy, although increasing resistance is of concern for longer-term treatment of disseminated disease. Continuing parenteral antibiotics to complete a therapeutic course should be considered, particularly in areas with known increased resistance to oral cephalosporins." (Added April 2013)

Page 91, Item 39: This question has been invalidated as a result of postpublication analysis and/or new data that are relevant to the question. Please select answer C to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. This item has been excluded because the original question did not mention that the patient had hemoptysis, which, in combination with her other clinical findings, suggests pulmonary vasculitis and the need for a diagnostic open lung biopsy. (Added April 2013)

Page 93, Item 48: The SI unit conversion for the C4 value should be 86 mg/L, not 860 mg/L. (Added June 2014)

Page 117, Item 23: At the end of the first paragraph, "...and it does not cause constipation" has been deleted because constipation is a possible side effect of tramadol. (Added November 2014)

Page 128, Item 47: In the second paragraph, metatarsophalangeal is incorrect and has been changed to metacarpophalangeal. (Added November 2015)

MKSAP 16 Self-Assessment Updates

Update 4, Infectious Disease Item 8: This question has been invalidated. Please select Answer B to earn a point for this item and ensure completion of all items in this self-assessment examination, which is necessary for CME/MOC submission. Based on careful review of the item, it is clear that both female sex and maintaining an open drainage system can increase the risk for a catheter-associated urinary tract infection. (Added November 2015)

Invalidated Questions

The following questions have been invalidated as a result of postpublication analysis and/or
new data that are relevant to the question: Item 2, item 12, item 38, and item 103 from Cardiovascular Medicine; item 7 and item 41 from General Internal Medicine; item 114 from Hematology and Oncology; item 54 and item 97 from Infectious Disease; item 31 and item 48 from Nephrology; item 11 from Neurology; item 65 from Pulmonary and Critical Care Medicine; item 39 from Rheumatology; and item 8 from Update 4, Infectious Disease.

Footnotes

Cholesterol Management Guideline Updates

In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) jointly released new cholesterol guidelines, supplanting the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines published in 2002. The major changes from the previous guidelines are outlined below.

Cholesterol management: Compared with ATP III, the new recommendations base treatment of hyperlipidemia on a person’s risk for developing atherosclerotic cardiovascular disease (ASCVD) instead of the level of LDL cholesterol or other lipid measurement. (Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Nov 12. [Epub ahead of print] [PMID: 24222016])

The four groups expected to benefit from statin therapy include patients who have any of the following:

Clinical ASCVD

LDL cholesterol ≥190 mg/dL (4.92 mmol/L)

Diabetes mellitus and age 40 to 75 years with an LDL cholesterol of 70 to 189 mg/dL (1.81-4.90 mmol/L) and no ASCVD

No ASCVD or diabetes and estimated 10-year ASCVD risk ≥7.5%

The 10-year risk for ASCVD is estimated by using the Pooled Cohort Equations, which were derived from data from multiple longitudinal study databases, including the Framingham cohort.

For patients in any one of the four statin benefit groups, therapy with a statin is indicated, with the intensity determined by specific group, age, whether the LDL cholesterol is ≥190 mg/dL (4.92 mmol/L), and the 10-year risk for ASCVD.

High-intensity statin therapy is recommended for patients with LDL cholesterol of ≥190 mg/dL (4.92 mmol/L) if <75 years of age; ASCVD if <75 years of age; or diabetes if 40-75 years of age with an LDL cholesterol of 70 to 189 mg/dL (1.81-4.90 mmol/L) and 10-year ASCVD risk ≥7.5%.

Moderate-intensity statin therapy is recommended for patients with ASCVD if >75 years of age; or in patients with diabetes if 40-75 years of age with an LDL cholesterol of 70-189 mg/dL (1.81-4.90 mmol/L) and 10-year risk <7.5%. Patients without an LDL cholesterol of ≥190 mg/dL (4.92 mmol/L), ASCVD, or diabetes, but who have 10-year risk ≥7.5%, should be treated with moderate- to high-intensity statin therapy depending on the presence of comorbidities.

For patients with LDL cholesterol levels <190 mg/dL (4.92 mmol/L) who are not in one of the above groups, additional risk factors as well as physician and patient preference may be considered to inform treatment decisions. For example, the physician and patient may decide together to initiate statin therapy if the patient has a strong family history of ASCVD, even if the patient is not in one of the four statin benefit groups.

High-intensity statin therapy lowers LDL cholesterol on average by approximately ≥50%. Moderate-intensity statin therapy lowers LDL cholesterol on average by approximately 30% to ≤50%.

Statins are preferred for therapy since they were used in the primary trials showing benefit from pharmacotherapy, and there is less evidence for using other lipid-lowering drugs, including fibrates, niacin, bile acid sequestrants, and ezetimibe. Despite the limited evidence for the use of these non-statin drugs, they are sometimes prescribed when patients are intolerant of statins.

This major change from previous cholesterol guidelines was prompted by the observation that the key studies showing the benefit of treating hyperlipidemia used fixed doses of statins and did not vary these doses to reach specific target LDL cholesterol levels, the beneficial effects of statin therapy were not related to pretreatment LDL cholesterol levels, and those with the greatest benefit were those at high risk for ASCVD even if LDL cholesterol was not high. For patients at low risk for ASCVD, benefit was limited even if the LDL cholesterol was significantly elevated. Therefore, the new guidelines recommend that treatment decisions be based on the patient's likely benefit rather than on a pretreatment or target LDL cholesterol level.

ATP III recommendations state that the metabolic syndrome should be considered a secondary target for risk reduction therapy, but metabolic syndrome was not specifically addressed in the 2013 ACC/AHA guidelines.

The Eighth Joint National Committee (JNC 8) guidelines for the management of high blood pressure were published in late 2013 and provide evidence-based recommendations for treatment of patients with hypertension. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520. Erratum in: JAMA. 2014;7;311(17):1809. [PMID: 24352797]

Primary JNC 8 recommendations are summarized below:

In the general adult population <60 years of age, pharmacologic treatment is recommended when the systolic BP is ≥140 mm Hg or the diastolic BP is ≥90 mm Hg. The goal of therapy should be <140/90 mm Hg.

In patients ≥60 years of age, therapy is recommended if the systolic BP is ≥150 mm Hg or the diastolic BP is ≥90 mm Hg. The goal of treatment is <150/90 mm Hg, although patients with a BP of <140/90 mm Hg on well-tolerated therapy do not need to have their treatment changed.

The initiation threshold and goal for pharmacologic treatment in those ≥18 years of age with diabetes mellitus or chronic kidney disease is 140/90 mm Hg (which differs from the previously recommended level of 130/80 mm Hg). The American Diabetes Association (ADA), however, recommends a threshold and goal of 140/80 mm Hg in patients with diabetes mellitus.

In the general non-black population, thiazide diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs) all may be considered for initial treatment of hypertension, and all reduce the complications of hypertension. The JNC 8 guidelines include patients with diabetes mellitus in this recommendation.

For black patients, initial therapy should be a thiazide diuretic or CCB, including those with diabetes mellitus. As a group, black patients have less BP reduction with equivalent ACE inhibitors dosing compared with non-black patients. Furthermore, black patients initially treated with ACE inhibitors rather than CCBs have about a 50% higher rate of stroke, and combined cardiovascular outcomes are better with a thiazide diuretic than with an ACE inhibitor.

For all patients (regardless of race or the presence or absence of diabetes mellitus) >18 years of age with chronic kidney disease (including those with and those without proteinuria), initial therapy should be an ACE inhibitor or ARB because these agents are renoprotective and improve renal outcomes. In black patients with chronic kidney disease but without proteinuria, the initial agent can be a CCB, thiazide diuretic, ACE inhibitor, or ARB. If the initial choice is not an ACE inhibitor or ARB, then one of these should be the second drug added if necessary to lower the BP to target (<140/90 mm Hg).

In addition, any mentions of "2008 Surviving Sepsis guidelines" should be updated to read "2012 Surviving Sepsis guidelines." This correction appears in the following locations in Pulmonary and Critical Care Medicine: